Degree of reduction in normal liver complication probability from free-breathing to breath-hold liver SBRT: A dose-escalation strategy using radiation dose-volume effect

Introduction: This study aimed to analyze the degree of reduction in normal liver complication probability (NTCP) from free-breathing (FB) to breath-hold (BH) liver SBRT. The effect of the radiation dose-volume on the mean liver dose (MLD) was also analyzed due to dose prescription, normal liver volume (NLV), and PTV. Materials and Methods: Thirty-three stereotactic body radiation therapy (SBRT) cases of hepatocellular carcinoma were selected, retrospectively. For FB, the treatments were planned on average intensity projection scan (CTavg), and patient-specific internal target volume (ITV) margins were applied. To simulate the BH treatment, computed tomography (CT) scan correspond to the 40% - 50% of the respiratory cycle (CT40%-50%) was chosen, and an appropriate intrafraction margin of 2 mm, 1.5 mm, and 1.5 mm were given in craniocaudal (CC), superior-inferior (SI), and lateral direction to generate the final iGTV. As per RTOG 1112, all organs at risk (OAR’s) were considered during the optimization of treatment plans. NTCP was calculated using LKB fractionated model. Multivariate regression analysis was performed to see the effect of EQD2Gy, NLV, and PTV on MLD2Gy. Results: A significant dosimetric difference was observed in the normal liver (liver-ITV/iGTV). A reduction of 1.7% in NTCP was observed from FB to BH technique. The leverage of dose escalation is more in BH because MLD2Gy corresponds to 5%, 10%, 20%, and 50% NTCP was 0.099 Gy, 0.41 Gy, 1.21 Gy, and 3.432 Gy more in BH as compared to FB technique. In MVRA, the major factor which was attributed to a change in MLD2Gy is EQD2Gy. Conclusion: From FB to BH technique, a significant reduction in NTCP was observed. The dose prescription is a major factor attributed to the change in MLD2Gy. Advances in knowledge: If feasible, prefer BH treatment either for tumor dose escalation or for the reduction in NTCP.

Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals

Background Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). Methods In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication—hepatic decompensation or hepatocellular carcinoma (HCC)—or requiring liver transplant after SVR. Results During a median (Q1–Q3) follow-up of 31.6 (22.7–36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28–9.12]), pretreatment CPT class B or C (62.5 [3.08–1246.42]) and MELD scores (1.37 [1.03–1.82]), CPT class B or C at SVR (10.71 [1.32–87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49–13.15]), FIB-4 index at SVR (1.39 [1.13–1.70]), and LS at SVR (1.05 [1.02–1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. Conclusions LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.